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Research: Landscape of microRNA and target expression variation and covariation in single mouse embryonic stem cells
- Marcel Tarbier,
- Sebastian D. Mackowiak,
- Vaishnovi Sekar,
- Franziska Bonath,
- Etka Yapar,
- Bastian Fromm,
- Omid R. Faridani,
- Inna Biryukova,
- and Marc R. Friedländer
Genome Res. February 2026 36: 291-302; Published in Advance January 12, 2026, doi:10.1101/gr.279914.124
...-to-mRNA ratios, whereas the reverse holds for proteins that are more variable (Methods) (Fig. 6D, left). Further, when estimating the ratio of RNA to protein, we found that the targets of miR-17 and miR-302, both abundant in human embryonic stem cells, are lower than for background genes (Fig. 6D, right...
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Research: Transcriptional modulation unique to vulnerable motor neurons predicts ALS across species and SOD1 mutations
- Irene Mei,
- Susanne Nichterwitz,
- Melanie Leboeuf,
- Jik Nijssen,
- Isadora Lenoel,
- Dirk Repsilber,
- Christian S. Lobsiger,
- and Eva Hedlund
Genome Res. September 2025 35: 1975-1991; Published in Advance July 17, 2025, doi:10.1101/gr.279501.124
...stem cell–derived SOD1E100G MNs and shows that dysregulation of VGF, INA, and PENK is a strong disease predictor across species and SOD1 mutations. Our study reveals MN population-specific gene expression and temporal disease-induced regulation that together provide a basis to explain ALS selective...
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Method: Multicondition and multimodal temporal profile inference during mouse embryonic development
- Ran Zhang,
- Chengxiang Qiu,
- Galina N. Filippova,
- Gang Li,
- Jay Shendure,
- Jean-Philippe Vert,
- Xinxian Deng,
- William Stafford Noble,
- and Christine M. Disteche
Genome Res. October 2025 35: 2339-2351; Published in Advance August 14, 2025, doi:10.1101/gr.279997.124
...and multimodal profiles across time, and extrapolate single-cell profiles in a missing modality. We apply Sunbear to reveal sex-biased transcription during mouse embryonic development and predict dynamic relationships between epigenetic priming and transcription for cells in which multimodal profiles...
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Research: ZSWIM8 destabilizes many murine microRNAs and is required for proper embryonic growth and development
- Charlie Y. Shi,
- Lara E. Elcavage,
- Raghu R. Chivukula,
- Joanna Stefano,
- Benjamin Kleaveland,
- and David P. Bartel
Genome Res. September 2023 33: 1482-1496; Published in Advance August 2, 2023, doi:10.1101/gr.278073.123
...in Drosophila, in which point mutants in the Zswim8 ortholog Dora are lethal (90%–100% penetrance, depending on the allele and genetic background), with most individuals dying during embryonic or early larval development (Kingston et al. 2022). In contrast, mutants of the C. elegans ortholog, ebax-1...
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Research: Common cis-regulatory variation modifies the penetrance of pathogenic SHROOM3 variants in craniofacial microsomia
- Hao Zhu,
- Jiao Zhang,
- Soumya Rao,
- Matthew D. Durbin,
- Ying Li,
- Ruirui Lang,
- Jiqiang Liu,
- Baichuan Xiao,
- Hailin Shan,
- Ziqiu Meng,
- Jinmo Wang,
- Xiaokai Tang,
- Zhenni Shi,
- Liza L. Cox,
- Shouqin Zhao,
- Stephanie M. Ware,
- Tiong Y. Tan,
- Michelle de Silva,
- Lyndon Gallacher,
- Ting Liu,
- Jie Mi,
- Changqing Zeng,
- Hou-Feng Zheng,
- Qingguo Zhang,
- Stylianos E. Antonarakis,
- Timothy C. Cox,
- and Yong-Biao Zhang
Genome Res. May 2025 35: 1065-1079; Published in Advance April 15, 2025, doi:10.1101/gr.280047.124
...as one of the genetic modifiers that influence the penetrance of pathogenic variants (Castel et al. 2018). These common variants, which modify gene expression in specific haplotype combinations with rare pathogenic alleles, “interact” with the latter, thereby modulating their penetrance (Emison et al...
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Method: Early embryonic mutations reveal dynamics of somatic and germ cell lineages in mice
- Arikuni Uchimura,
- Hirotaka Matsumoto,
- Yasunari Satoh,
- Yohei Minakuchi,
- Sayaka Wakayama,
- Teruhiko Wakayama,
- Mayumi Higuchi,
- Masakazu Hashimoto,
- Ryutaro Fukumura,
- Atsushi Toyoda,
- Yoichi Gondo,
- and Takeshi Yagi
Genome Res. May 2022 32: 945-955; Published in Advance May 9, 2022, doi:10.1101/gr.276363.121
...cell positions (Fig. 2E, a-8, h-7, k-7, o-6, x-4, and β-4), where VAFs became essentially zero except for germ cell tissues, an average of 12.3 mutations were accumulated. Because it is known to take 12 cell divisions to go from a fertilized egg to PGC induction (corresponding to embryonic day 6...
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Research: Long-read transcriptome sequencing of CLL and MDS patients uncovers molecular effects of SF3B1 mutations
- Alicja Pacholewska,
- Matthias Lienhard,
- Mirko Brüggemann,
- Heike Hänel,
- Lorina Bilalli,
- Anja Königs,
- Felix Heß,
- Kerstin Becker,
- Karl Köhrer,
- Jesko Kaiser,
- Holger Gohlke,
- Norbert Gattermann,
- Michael Hallek,
- Carmen D. Herling,
- Julian König,
- Christina Grimm,
- Ralf Herwig,
- Kathi Zarnack,
- and Michal R. Schweiger
Genome Res. November 2024 34: 1832-1848; Published in Advance September 13, 2024, doi:10.1101/gr.279327.124
...′ splice-site usage. As a subunit of the U2 small nuclear ribonucleoprotein complex (snRNP), SF3B1 is UV cross-linked with the pre-mRNA on both sides of the branch-point (BP) adenosine in the A-complex, at nucleotide positions −6 and +5 (Gozani et al. 1996, 1998). The most common mutations in SF3B1...
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Method: Single-cell Rapid Capture Hybridization sequencing reliably detects isoform usage and coding mutations in targeted genes
- Hongke Peng,
- Jafar S. Jabbari,
- Luyi Tian,
- Changqing Wang,
- Yupei You,
- Chong Chyn Chua,
- Natasha S. Anstee,
- Noorul Amin,
- Andrew H. Wei,
- Nadia M. Davidson,
- Andrew W. Roberts,
- David C.S. Huang,
- Matthew E. Ritchie,
- and Rachel Thijssen
Genome Res. April 2025 35: 942-955; Published in Advance January 10, 2025, doi:10.1101/gr.279322.124
...the SF3B1 K700E mutation in CLL3 and CLL26 in both screening (S) and venetoclax-relapsed (R) samples (Supplemental Fig. S8A). This mutation was also confirmed by the WES data from these samples (Thijssen et al. 2022). In scRaCH-seq, the K700E mutation was consistently observed with an overall frequency...
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Research: Locus-resolution analysis of L1 regulation and retrotransposition potential in mouse embryonic development
- Patricia Gerdes,
- Dorothy Chan,
- Mischa Lundberg,
- Francisco J. Sanchez-Luque,
- Gabriela O. Bodea,
- Adam D. Ewing,
- Geoffrey J. Faulkner,
- and Sandra R. Richardson
Genome Res. September 2023 33: 1465-1481; Published in Advance October 5, 2023, doi:10.1101/gr.278003.123
...′ truncated and mutated (Voliva et al. 1983; Waterston et al. 2002), leaving approximately 2800 full-length L1s (Penzkofer et al. 2017). Ongoing L1 activity has generated substantial variation in L1 content among inbred strains, as well as interindividual variation in L1 content within strains (Akagi et al...
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Resource: Common and specific gene regulatory programs in zebrafish caudal fin regeneration at single-cell resolution
- Yujie Chen,
- Yiran Hou,
- Qinglin Zeng,
- Irene Wang,
- Meiru Shang,
- Kwangdeok Shin,
- Christopher Hemauer,
- Xiaoyun Xing,
- Junsu Kang,
- Guoyan Zhao,
- and Ting Wang
Genome Res. January 2025 35: 202-218; Published in Advance January 14, 2025, doi:10.1101/gr.279372.124
...common and cell-type-specific regeneration-responsive gene (RRG) programs and cis-regulatory elements, as well as key TFs associated with stages and cell types during regeneration, enhancing our understanding of tissue regeneration.ResultsSingle-nucleus multiomic profiling of zebrafish caudal fin...
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